PT Bio Farma, the sole World Health Organization-approved Indonesian vaccine producer, manufactures a whole-cell whooping cough vaccine (wP) that, as part of a pentavalent diphtheria-tetanus-pertussis/hepatitis B/Haemophilus influenzae b (DTP/HB/Hib) vaccine, is used in Indonesia and many other countries. We report here the whole-genome sequence for Bordetella pertussis Pelita III, PT Bio Farma’s wP production strain.

Pertussis or whooping cough is a disease caused by Bordetella pertussis bacteria, and the spread disease can be controlled by vaccination. Currently, some pertussis toxoids are prepared by chemical modification, which makes it possible to change the immunospecificity. To avoid altering the structure of toxoids, genetic modification is considered more harmless than chemical modification. A mutant of R9K/E129G is known to have lower toxicity and can be used as a component of the pertussis vaccine. However, the reason behind the low toxicity of this toxoid at the molecular level remains unclear. Hence, this study aimed to investigate the molecular mechanism behind the low toxicity of R9K/E129G using molecular dynamics simulation. The structure of the mutant was built using the homology modeling approach, and the behavior of wild-type and mutant toxoid were studied by molecular dynamics simulation for 300 ns. The changes in the structure in all systems were calculated by POVME, which was further investigated by molecular docking with NAD+ as the substrate. The results showed that the active site of the wild type was opened in the reducing environment while the mutant remained closed, which hindered the binding of NAD+. In conclusion, the dual mutation of R9K/E129G reduces pertussis toxoid's toxicity by preventing the catalytic site's opening. Therefore, this natural mutant can be further optimized in the development of a safer vaccine for pertussis. Keywords: Pertussis toxin, R9K/E129G mutant, molecular dynamics simulation, NAD+ binding site, vaccine.